"Every cell type has a different capacity to sense double-stranded RNA," the molecule that BO-112 mimics, Kalbasi added. However, these early results hint that BO-112 could be an effective strategy to take down tumors that are resistant to immunotherapy, they noted.
#Red pill 44 112 trial#
That said, "the number of patients is too low to draw a formal conclusion about the responses because the main objective of this first in-human clinical trial was safety," the authors wrote. Going viral: 6 new findings about viruses 5 things women should know about ovarian cancer In the clinical trial, BO-112 made tumors more sensitive to these two drugs after eight to 12 weeks of treatment, 10 patients with metastatic cancer reached "stable disease," meaning their tumors had stopped growing, while the tumors of three other patients actually began to shrink. These treatments "remove the brakes off the body’s T cells" so they can target tumors more effectively, Kalbasi said. Of the 44 patients, 28 patients who did not experience these side effects received injections of B0-112 along with existing immunotherapy drugs, called nivolumab and pembrolizumab. Related: 11 surprising facts about the immune system Most of the patients handled the treatment well, although three of the 44 participants experienced a severe reaction, including lung inflammation and a significant drop in platelet levels, which are important for blood clotting, according to the report. To probe whether B0-112 works in human patients as it does in mice, another group of researchers conducted a small clinical trial, sponsored by the pharmaceutical company Highlight Therapeutics. In mice with small tumors, the combinatory treatment was more effective, as the tumors shrunk more dramatically in size and sometimes disappeared altogether, he said. However, in mice with large tumors, the cancer eventually began to grow again, Kalbasi noted. "When we added BO-112, the tumors either decreased in size or stopped growing for a period of time," he said. However, after the injection, the T cell treatment suddenly worked, Kalbasi said. Without an injection of BO-112, the lab mice's tumors did not succumb to adoptive T cell therapy, because the T cells could not detect the tumors in the first place. Similar to NLRC5, the drug makes cancer cells produce antigens rather than switching on a specific gene, the drug instead tricks the tumor into reacting as if it's being infected by a virus. To achieve the same result more practically, the team turned to BO-112. The same strategy worked when the team moved from lab dishes to actual lab mice however, for the same approach to work in humans, scientists would need to somehow turn on the NLRC5 gene in a patient's tumor cells. Activating this gene made the tumor cells visible to T cells, leaving the cancer open to attack. In lab dish studies, the mutant tumor cells could not be detected by T cells.īut when the team turned on a gene called NLRC5 in the engineered tumors, the cells generated antigens in spite of the other mutations they'd introduced. They first engineered mouse tumor cells with mutations that would reduce the number of antigens on their surfaces. In theory, forcing such tumors to build and present antigens on their surface would make them visible to T cells Kalbasi and his colleagues tested this idea in several mouse studies. These T cells detect tumors by scanning for specific molecules on their surfaces, called antigens - but some tumors can slow or stop production of these antigens, or prevent them from being displayed on a cell's surface, thanks to specific genetic mutations, making them effectively invisible to T cells.
Cancer immunotherapy works by ramping up the body's immune defense against tumors, but cancer cells use various tricks to resist these attacks.įor instance, an immunotherapy called "adoptive T cell therapy" involves extracting a patient's immune cells, modifying them to better recognize specific tumors and then reintroducing them to the body, according to a statement.